THE WEAVER MUTANT MOUSE AS A MODEL OF NIGROSTRIATAL DYSFUNCTION

The weaver mutant mouse has a genetic defect that results in the loss of dopamine neurons in the nigrostriatal pathway. Striatal tyrosine hy droxylase and dopamine content are reduced by 60-70%, and dopamine upt ake is reduced by as much as 95%. Deficits in all three of these stria tal dopamine markers are seen as early as postnatal d 3. The striatal dopamine systems in the weaver apparently have the ability to compensa te for this dopamine deficit. Thus, in the weaver, in vitro resting re lease, as well as amphetamine-evoked fractional release of endogenous dopamine are increased. An additional change seen in the weaver striat um is an elevated serotonin content. These alterations may play an ada ptive role in attempting to compensate for the dopamine loss. In summa ry, the weaver mutant mouse has dramatic deficits in the nigrostriatal pathway, but also seems to develop certain adaptive mechanisms in dop aminergic and other transmitter systems that may compensate functional ly for the dopamine deficit. Thus, the weaver mouse provides a unique animal model for studying naturally induced neuronal degeneration that complements those models using surgical and pharmacological protocols .